VZV ORF63 protects human neuronal and keratinocyte cell lines from apoptosis and changes its localization upon apoptosis induction

Abstract

BACKGROUND: There are many facets of varicella zoster virus (VZV) pathogenesis that are not fully understood, such as the mechanisms involved in the establishment of lifelong latency, reactivation and development of serious conditions such as post herpetic neuralgia (PHN). Virus-encoded modulation of apoptosis has been suggested to play an important role in these processes. VZV open reading frame (ORF) 63 has been shown to modulate apoptosis in a cell type specific manner, but the impact of ORF63 on cell death pathways has not been examined in isolation, in the context of human cells.

RESULTS: We sought to elucidate the effect of VZV ORF63 on apoptosis induction in human neuron and keratinocyte cell lines. VZV ORF63 was shown to protect differentiated SH-SY5Y neuronal cells against staurosporine-induced apoptosis. In addition, VZV infection did not induce high levels of apoptosis in the human keratinocyte cell line, HaCaTs, highlighting a delay in apoptosis induction. VZV ORF63 was shown to protect HaCaTs against both staurosporine and Fas ligand induced apoptosis. Confocal microscopy was utlilised to examine VZV ORF63 localisation during apoptosis induction. In VZV infection and ORF63 expression alone, VZV ORF63 became more cytoplasmic with aggregate formation during apoptosis induction.

CONCLUSION: Together this suggests VZV ORF63 protects both differentiated SH-SY5Ys and HaCaTs from apoptosis induction and may mediate this effect through its localization change during apoptosis. VZV ORF63 is a prominent VZV gene product in both productive and latent infection and thus may play a critical role in VZV pathogenesis through aiding neuron and keratinocyte survival.